Research funding for newborn health and stillbirths, 2011–20: a systematic analysis of levels and trends

Summary Background Worldwide, an estimated 4·4 million newborn deaths and stillbirths occurred in 2020, and 98% of these deaths occurred in low-income and middle-income countries (LMICs). We aimed to analyse new research grants for newborns and stillbirth awarded by major funders in 2019–20, and all research funding allocated to LMIC-based institutions in 2011–20. Methods For this systematic analysis, we searched Dimensions, the world's largest research funding database, for grants relevant to neonatal and stillbirth research. Included grants were categorised by in-depth content analysis, with descriptive quantitative analyses by funder and recipient countries, research pipeline, topic, and year. Findings Globally, in 2019–20, major funders awarded a mean annual total of US$577·1 million per year for newborn and stillbirth research (mean total of 550 grants per year). $166·3 million (28·8%) of $577·1 million was directed to small and vulnerable newborn research, but only $8·4 million (1·5%) was directed to stillbirth research. The majority of funding, $537·0 million (93·0%), was allocated to organisations based in high-income countries. Between 2011 and 2020, LMIC-based recipients were named on 1985 grants from all funders worth $486·7 million, of which $73·1 million (15·0%) was allocated to small and vulnerable newborn research and $12·0 million (2·5%) was allocated to stillbirth research. Most LMIC funding supported preclinical or observational studies ($236·8 million [48·7%] of $486·7 million), with implementation research receiving only $13·9 million (2·9%). Interpretation Although investment in research related to neonatal health and stillbirths has increased between 2011 and 2020, there are marked disparities in distribution geographically, between major causes of mortality, and among research pipeline types. Stillbirth research received minimal funding in both high-income countries and LMICs, despite a similar number of deaths compared with neonates. Direct investment in LMIC-led research, especially for implementation research, could accelerate the slow global progress on stillbirth prevention and newborn survival. Funding None. Translations For the French, German and Spanish translations of the abstract see Supplementary Materials section.


The Dimensions database
• Dimensions is an interlinked research information system provided by Digital Science https://www.dimensions.ai/• It uses automated AI-supported methods to collate funding data from open-access web-based sources and is updated on a monthly basis • It is not actively restricted to English, and lists automatic translation of abstracts when provided in another language • The database allows the use of keywords and Boolean search terms to identify relevant grants, similar to online databases of scientific publications • At the time of publication, the database includes more than 7 million grants worth more than 2.3 trillion USD from 669 funders worldwide • Available grant information includes the title, abstract, funding amount, start and end dates, and the name and location of funders and recipients • As Dimensions sources data from funder platforms it lists only a single funder for each grant but can list multiple recipients • Grant funding amounts are obtained in their original currencies as well as converted to US dollars, on the basis of the exchange rate at the time of the start date of the grant; in the case that a yearly distribution of the funding amount is provided (eg US National Institutes of Health projects), the funding amount is converted for each year's exchange rate

Search strategy used to search the Dimensions database
We searched the Dimensions database using the following search strategy: 'newborn* OR neonat* OR baby OR babies OR infant* OR stillbirth* OR stillborn* OR deadborn* OR "dead born" OR "dead borns" OR "fetal death" OR "fetal deaths" OR "fetal demise" OR "foetal death" OR "foetal deaths" OR "foetal demise" OR "fetal mortality" OR "foetal mortality" OR "perinatal death" OR "perinatal deaths" OR "perinatal mortality" OR "intrapartum death" OR "intrapartum deaths" OR "intrapartum demise" OR "intrapartum mortality" OR "intrapartum death" OR "intra-partum deaths" OR "intra-partum demise" OR "intra-partum mortality" OR "intrauterine death" OR "intra-uterine death" OR "intrauterine deaths" OR "intra-uterine deaths" "small vulnerable newborn" OR "small vulnerable newborns" OR "small and vulnerable newborn" OR "small and vulnerable newborns" OR "small sick newborn" OR "small sick newborns" OR "small and sick newborn" OR "small and sick newborns" OR "low birth weight" OR "low birthweight" OR LBW OR "small for gestational age" OR SGA OR "fetal growth restriction" OR FGR OR "intrauterine growth restriction" OR "intra-uterine growth restriction" OR IUGR OR preterm OR pre-term' in title and abstract;

Table S1. Categorisation of included grants by thematic area of the described research activity
Categorisation of grant thematic areas was adapted from the major causes of neonatal mortality as listed in Oza et.al (2014) (1) Grants were assigned up to two thematic areas with equal weighting.

Table S2. Categorisation of included grants by research pipeline
Research pipeline category Inclusive of (but not limited to) study types: Grants were assigned up to two pipeline categories with equal weighting.

Illustrative examples of included grants and categorisation
(a) Single funder, single recipient The below example illustrates a grant from a single funding institution to a single research organisation which has a focussed research theme related to 'Preterm direct complications' and lies in the 'Basic science, pre-clinical research, technology development' part of the research pipeline. grant.9294008

Sex as biological variable in Bronchopulmonary Dysplasia: Role of the Notch pathway
Bronchopulmonary dysplasia (BPD) is a debilitating lung disease with long-term consequences and is one of the most common causes for morbidity in premature neonates.Postnatal exposure to high concentrations of oxygen (hyperoxia) contributes to the development of BPD.Despite the well-established sex-specific differences in the incidence of BPD and impaired lung function in males, the molecular mechanism(s) behind these are not completely understood.Our laboratory has been focused on the study of sex-specific differences in neonatal hyperoxic lung injury.Aberrant Notch signaling contributes to the pathogenesis of many chronic lung diseases and Notch activation is seen in lungs of human infants with BPD.The role of aberrant Notch signaling in pulmonary dysangiogenesis in BPD has not been determined.Critically, neonatal female mice have improved alveolarization and pulmonary vascular development, which is associated with, decreased Notch pathway activation and expression of the Notch ligand Dll4 compared to male littermates in a murine model of BPD.The overall aim of this innovative proposal is to define the role of sex-specific activation of Notch pathway in modulating pulmonary angiogenesis in neonatal hyperoxic lung injury.We hypothesize that decreased Notch activation secondary to lesser Dll4 expression preserves pulmonary angiogenesis in female neonates .The above hypothesis will be tested by the following specific aims: Aim 1: Elucidate the spatio-temporal role of endothelial DLL4 (Notch ligand) in modulating pulmonary angiogenesis.Aim 2: Determine the role pulmonary endothelial Notch signaling in modulating pulmonary angiogenesis in the developing lung exposed to hyperoxia.This proposal will address knowledge gaps in the molecular mechanisms behind the sexual divergent incidence of bronchopulmonary dysplasia and lay the foundation for future sex-specific treatment strategies.The below example illustrates a grant by a single funding institution to multiple recipient research organisations.
It has a focussed research theme related to 'Neonatal infections' but describes two pipeline elements: 'Basic science, pre-clinical research, technology development' ("to dissect the pathological and immune mechanisms involved", "to characterize [..] genetically the infecting parasites, providing a structural basis for anti-PAM vaccine design") and 'Observational clinical research, epidemiology' (..."the immunological effects will be measured in the…newborns, and in the infant, in relation with timing of infection").).

grant.3780035 Strategies To Prevent Pregnancy-Associated Malaria
The Partners propose to conduct a cohort study in pregnant women and their newborns to quantify the effects of Pregnancy-Associated Malaria (PAM) and to identify a PAM vaccine candidate.Effects of PAM on the pregnant woman (placental infection and anaemia), the offspring (birth weight reduction), and the infant (increased morbidity and mortality) are well known.Studies underlined the role of P. falciparum variable surface antigens expressed on infected erythrocytes in binding to placenta.A specific immune response against this antigen reduces the effect of PAM during latter pregnancies, making possible to develop a new preventive strategy based on the enhancement of this specific response.This goal will be achieved through cohort studies in 2 endemic areas (West and East Africa), as the mechanisms and the resulting effects may vary with transmission.Biological samples will be collected during pregnancy and infancy to dissect the pathological and immune mechanisms involved, as well as to characterize phenotypically and genetically the infecting parasites, providing a structural basis for anti-PAM vaccine design.The immunopathological effects will be measured in the mothers, their newborns, and the infant, in relation with timing of infection.The ultimate goal is to identify the most immunogenic epitopes of VAR2CSA (the major variable surface antigens of P. falciparum parasites infecting the pregnant women) to be included in such a vaccine.It is anticipated that the product of this project will be directly usable to enter in the pipeline of vaccine development.The 7 Partners of the consortium (5 from 4 EU countries, and 2 from Benin and Tanzania) have a combined history of high class, internationally-recognized research in malaria.All EU teams have huge experience of collaboration with malaria endemic countries institutions and with studies related to malaria in pregnant women, that are also routinely conducted by the 2 African Partners.The below example illustrates a grant by a single funding institution to a single recipient research organisation.The research theme relates to 'Preterm direct complications' and it is an example of a grant we categorised as 'Implementation research, complex evaluation, health systems research' as it evaluates implementation of an intervention that has an existing evidence base for benefit and is being adapted for implementation in a specific population.This grant is also illustrative of the 5•1% (345/6,790) of grants in the Objective 2 dataset that did not provide the monetary value of the award and were our direct request to the funders to provide this information (following up over 5 months) was not successful in supplementing this information.We thus included this grant in any analysis of grant numbers but it did not contribute to analysis of funding amounts.

grant.9231225
Breastfeeding in premature infants: the impact of bfhi for neonatal units Each year are born premature 15 million worldwide, and Brazil is one of the ten countries with the highest number of premature births, a rate of 9.2% in 2010.Between 2007-2012, the increase in prematurity rate was due mainly to the higher number of cesarean section.Despite advances in neonatal care technologies and subsequent increased survival of these premature infants, prematurity contributes to 45% of deaths among newborns in Brazil.Currently, prematurity and its complications are the leading cause of neonatal mortality and morbidity.The impact in the short and long term of prematurity and its implications is stressful for parents and result in a high cost to the health system in Brazil.
Exclusive breastfeeding (EBF) is an important intervention with low cost to reduce neonatal morbidity and mortality, preventing infections and necrotizing enterocolitis, promoting optimal growth and neurodevelopment and encouraging the mother-baby bond.However, AME rates remain low among premature infants in Brazil, occurring frequently, weaning before discharge.Breastfeeding hospitalized premature is a major challenge due to its physiological and neurological immaturity and difficulty coordinating sucking, swallowing and breathing.Prolonged hospitalization in the neonatal unit can also generate the mother feelings of inadequacy and emotional stress, which can decrease lactation, difficult mother-child bond and delay the initiation of breastfeeding.The systematic and continuous support to mothers by trained professionals is essential to initiate and maintain maternal lactation and maintenance of exclusive breastfeeding until the sixth month of life.
Brazil is internationally recognized for developing initiatives to increase breastfeeding rates and policies have been implemented to promote, protect and support the AME, including the Baby-Friendly Hospital Initiative (BFHI).BFHI is a global strategy that aims to transform the practices, policies and structures of health services to support breastfeeding through implementation of the Ten Steps to Successful Breastfeeding and adoption of the International Code of Substitutes Marketing Breastmilk.BFHI was widely adopted in Brazil and has resulted in significant improvement in support of the initiation and duration of exclusive breastfeeding.However, BFHI was originally designed to support the EBF in newborns healthy term in maternity wards, and does not consider the complex and high technological density of neonatal units context as well as the difficulties in breastfeeding premature.Thus, despite national and strategies to encourage breastfeeding policies, premature are often deprived of the benefits of exclusive breastfeeding, the promising potential is predictable an innovative intervention that is in BFHI adapted for this population segment risk, called ten Steps to Successful Breastfeeding Exclusive in neonatal units, BFHI-Neo, whose effectiveness will be tested in Brazil with this design proposes its implementation focused on changing practices in Brazilian neonatal units mediated by the knowledge transfer of reference.The goal is to increase the early onset and the prevalence of exclusive breastfeeding; improve the early health conditions related to AME; improve practices to enhance the mother-baby bond and protect, promote and support the EBF in neonatal units.The ten hospitals / maternity (05 intervention and 05 control) selected to participate in the project are: 1) public or licensed to the Unified Health System, 2) regional reference in care delivery and newborn, 3) with Hospital title Child Friendly or participant's strategy Stork Network of the Ministry of Health, 4) with high rates of prematurity and 5) are located in five regions of the country: north, northeast, Midwest, southeast and south.
The effectiveness of any clinical intervention, including BFHI-Neo, will depend on the implementation and use of intervention by health professionals in practice.The PARIHS model focuses on the relationship between the nature of evidence, the context in which the shift is implemented and the way in which the change is facilitated.The model will guide the use of EPIC, multifaceted intervention knowledge transfer to promote change practices and behavior of health professionals.The successful implementation of BFHI-Neo also requires a strategic plan, with systematic evaluation to monitor the practical improvements and the improvement of care, as well as performed with the original BFHI.Health Practitioners in Quebec, Canada, have developed an electronic program to measure adherence to BFHI originates.These instruments were adapted to measure the adherence to new standards and criteria as the Ten Steps and Three Guiding Principles of BFHI-Neo.These instruments are being tested in a pilot study in Canada and Sweden, and will facilitate data collection, analysis and dissemination of the results of the level of adherence to the BFHI-Neo.
The executor multidisciplinary project team brings together researchers and practitioners with extensive experience in scientific production and care to premature and family and breastfeeding.undergraduate students and graduate students and technicians will be included in the study to provide logistical support.The project includes collaboration with researchers from Canada and Sweden, which developed the BFHI-Neo and their assessment tools, and who also have expertise in knowledge transfer and PARIHS model.The project coordinator has ties and collaboration with strategic professionals and researchers in the participating institutions, which is essential for the successful implementation of BFHI-Neo.The development of research in each region will be the responsibility of a regional coordinator and operational staff.The project monitoring will be done through programs activities in all operational phases of the project, monthly reports, monthly in-person meetings and video conferences, or more frequent, with the participation of the general and regional coordination.Budget execution of the project will be the responsibility of coordinating with the financial support technical assistance from the Ribeirão Preto School of Nursing, University of São Paulo (EERP-USP) and the researchers regional project coordinators.

Start date 2013-12-13
End Table S5.Funding awarded was assumed to be evenly distributed across categories and recipients, where grants covered multiple categories or awarded to more than one organization.Since up to two thematic and research categories could be coded for each grant, their total proportions can exceed 100%.Active funding takes into account all available funding per year, under the assumption that grants are evenly dispersed across their duration, with totals apportioned to that available between 2011 and 2020.
11. Table S6 319,200 (445,040 -3,898,449) Table S7: Funding amounts and numbers of grants presented for each category are the mean of those newly awarded by all funders in 2019 or 2020.In total, 163 new grants worth $82,495,313 and 104 new grants worth $66,128,514 with at least one LMIC-hosted recipient organization were awarded by all funders in 2019 and 2020 respectively.Median award sizes for each category are based on the portion of awards available between 2011 and 2020 only.Grants may be relevant to more than one overall thematic category (and therefore the sum of proportions for overall thematic categories may exceed 100%).Otherwise, where grants were related to multiple theme or pipeline categories, or were awarded to more than one organization, they were assumed to be evenly apportioned.
The study objectives are to implement and test the effectiveness of the Three Principles and the Ten Steps to Successful BFHI-Neo Breastfeeding and use PARIHS model (Promoting Action on Research Implementation in Health Services) of the transfer of knowledge and multifaceted and interactive strategy EPIC (Evidence-based practice Identification & change) to promote and support changes in breastfeeding practices in neonatal units in Brazil.Expected to contribute new evidence for the adoption of new national public policies related to breastfeeding in neonatal units.
14. Figure S2.Bubble graph demonstrating relationship between neonatal mortality burden (mean annual neonatal deaths per 1000 live births) and total research investments received by LMIC institutions from 2011-2020.

Figure S2 :
Figure S2: Mean neonatal mortality rate (2011-2020) (NMR) as defined by neonatal deaths per 1000 live births according to UN IGME data and total research investments received by LMIC institutions from 2011-2020 (funding amount and number of grants plotted are those specific to LMIC institutions and any funding apportioned to grant partners in HIC is not included here), with bubble size representative of number of grants received.NB: grant financial information was unavailable for 5.1% (345/6,790) of grants.

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The 672 funders of grants listed in the Dimensions database as of June 2023 are provided below 1 : Host countryWe searched PubMed/MEDLINE on 17 October 2022 for publications from 16 Feb 2016 onwards, updating a previously conducted version of this search (EJA Fitchett masters thesis, Harvard University) using the following search terms: , and if needed full texts, were screened for relevance to the study topic by EL or PA.
Active Year is 2020 or 2019 or 2018 or 2017 or 2016 or 2015 or 2014 or 2013 or 2012 or 2011.

Thematic area Inclusive of (but not limited to) research related to:
-Congenital infections including: malaria, Zika, cytomegalovirus -COVID-19 newborn infection and congenital maternal to newborn infection -Neonatal HIV/ vertical transmission of HIV -Hepatitis B virus (HBV) vertical transmission -Neonatal vaccination (e.g.BCG, HBV)

Table S3 . List of funders of included grants
= funder identified as major funder of newborn health and stillbirth research (awarded ≥15 grants worth $5 million or ≥75 grants worth ≥$1 million with newborn health or stillbirth terms in the grant abstract) and featured in the 2019-2020-restricted Objective 1 dataset but did not feature in the Objective 2 dataset which was restricted to grants active between 2011-2010 and awarded to at least one LMIC hosted recipient. *

Table S4 .
Mean annual funding awarded by major funders (2019-2020) -all recipients.Major funders were defined as funders of ≥15 grants worth $5m USD or ≥75 grants worth ≥$1m USD with newborn search terms in the Dimensions database.Funding awarded was assumed to be evenly distributed across categories and recipients, where grants covered multiple categories or awarded to more than one organization.Since up to two thematic and research categories could be coded for each grant, their total proportions can exceed 100%.Sustainable Development Goal (SDG) region country allocations available at: https://unstats.un.org/sdgs/indicators/regional-groups[accessed 5.1.2023]

13. Table S8. Total funding (USD) active between 2011-2020 awarded to at least one LMIC recipient, number of active grants and median available funding per grant (USD) and interquartile range (IQR), by recipients and funder
(3) funding amount was missing for 69 grants.Countries of recipients were categorised according to Sustainable Development Goal (SDG) region(2)and World Bank economic status(3)